The objective of this proposal is to determine if there is a subgroup of depressive illnesses characterized by an abnormality in Vmax or Km of platelet serotonin (5-HT) uptake. This group of patients may be related to the depressed patients previously reported to have diminished 5-hydroxy-indoleacetic acid (5-HIAA) in CSF, exacerbation after para-chlorophenylalanine treatment and improvement on 5-hydroxytryptophan and chlorimipramine. We will also measure platelet 5-HT uptake in first-degree relatives in other patient groups and controls, determining norms and effect of sex, age, diurnal factor and variations during the month. The effect of treatment with tricyclic antidepressants and lithium on platelet 5-HT uptake will be studied. The relationship between response to tricyclics and 5-HT uptake will be studied. The relationship between 5-HT and CSF 5-HIAA, platelet 5-HT levels and platelet monoamine oxidase will be studied.